DESCRIPTION: (Adapted from the Applicant=s Abstract) Cyclic nucleotide gated (CNG) ion channels and second messenger pathways that play an important role i odor transduction are also used during development to regulate the connectivit of olfactory receptor neurons. This proposal is to study the presence of these second messenger pathways in developing olfactory receptor neurons to gain insight into the mechanisms underlying the development of olfactory function, and possibly of neurons in general. The electrical properties of regenerating olfactory receptor neurons, in particular the time course of expression of voltage-activated channels, will be studied to provide a time line for the system. Second, preliminary evidence that CNG channels appear early in development will be expanded to delineate the physiological pathways that regulate these channels, with particular emphasis on possible regulation by th gaseous second messengers NO and CO. Finally, calcium imaging will be used to determine if activation of CNG channels allows calcium entry that is critical to implement developmental changes in these neurons. Knowledge about the precise mechanisms involved in the development of the olfactory system may yield new clinical insight into disorders associated with neuron replacement and functional repair following nerve injury.